title: Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials.
abstract: OBJECTIVE
  To report the long-term safety data of certolizumab pegol (CZP) in rheumatoid arthritis (RA) accumulated as of 30 November 2011.
  
  
  METHODS
  Data from 10 completed randomised controlled trials (RCT) of CZP in RA and several open-label extensions (OLE) were pooled across all doses. Reported adverse events (AE) occurred between the first dose and 84 days after the last dose. All deaths, serious infectious events (SIE) and malignancies were reviewed by external experts, classified according to predefined rules, and validated by an external steering committee. Incidence rates (IR) and event rates (ER) per 100 patient-years (PY) are presented.
  
  
  RESULTS
  4049 RA patients who received CZP were included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years (range 0.04-7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most common serious AE, occurring more frequently in CZP compared to placebo-treated patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65 to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER 4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and 70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY), including five lymphomas (IR 0.05/100 PY).
  
  
  CONCLUSIONS
  No new or unexpected safety signals associated with CZP emerged in this updated long-term safety analysis. While SIE rates were higher for CZP than for placebo in RCT, the rate decreased with continued exposure to CZP. These rates are consistent with data previously reported for CZP and other tumour necrosis factor inhibitors.
authors.affiliation: Hospital for Special Surgery, New York, New York, USA.
authors.forename: V P
authors.initials: VP
authors.lastname: Bykerk
authors.affiliation: Baylor Research Institute and Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cush
authors.affiliation: Oregan Health and Science University, Portland, Oregon, USA.
authors.forename: K
authors.initials: K
authors.lastname: Winthrop
authors.affiliation: Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: L
authors.initials: L
authors.lastname: Calabrese
authors.affiliation: IHU Imagine, Université Paris Descartes, Hôpital Necker Enfants malades, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: UCB Pharma SA, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: de Longueville
authors.affiliation: Department of Rheumatology, Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: van Vollenhoven
authors.affiliation: Université Paris-Sud, AP-HP, Hôpitaux universitaires Paris-Sud, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Mariette
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068582:Certolizumab Pegol; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol
keywords: Anti-TNF; Infections; Rheumatoid Arthritis; Tuberculosis